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Treatment with IP-10 induces host-protective immune response by regulating the T regulatory cell functioning in Leishmania donovani-infected mice

Medical Microbiology and Immunology, ISSN: 0300-8584, Vol: 200, Issue: 4, Page: 241-253
2011
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Article Description

Visceral leishmaniasis (VL), caused by the protozoan parasite, Leishmania donovani, is characterized by an infection in the liver and spleen. The failure of the Wrstline drugs has led to the development of new strategies for combating VL. Recently, our group has shown that interferon-γ-inducible protein (IP)-10, a CXC chemokine, renders protection against VL. In the present study, we have elucidated the mechanism by which IP-10 renders protection in in vivo L. donovani infection. We observed that IP-10-treated parasitized BALB/c mice showed a strong host-protective T helper cell (Th) 1 immune response along with marked decrease in immunosuppressive cytokines, tumor growth factor (TGF)-β, and interleukin (IL)-10 secreting CD4+ T cells. This IP-10-mediated decrease in immunosuppressive cytokines was correlated with the reduction in the elevated frequency of CD4+CD25+ T regulatory (Treg) cells along with the reduced TFG-β production from these Treg cells in Leishmania-infected mice. This reduction in TGF-β production was due to eVective modulation of TGF-β signaling by IP-10, which reduced the immunosuppressive activity of Treg cells. Thus, these Wndings put forward a detailed mechanistic insight into IP-10-mediated regulation of the Treg cell functioning during experimental VL, which might be helpful in combating Leishmania-induced pathogenesis. © Springer-Verlag 2011.

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